Breast cancer is by far the most common cancer among women with around 1 million women worldwide being diagnosed with the disease each year. In the UK alone around 45,500 women are diagnosed with breast cancer annually.
Currently all breast cancer patients are assessed for oestrogen receptor (ER) and progesterone receptor (PR) status to determine the suitability of respective patients for endocrine or hormonal therapy. Endocrine or hormonal therapies are agents used to treat women with breast cancer who have hormone receptors on their breast cancer cells which allow the binding of hormone and include anti-oestrogens, for example tamoxifen and fulvestrant, and aromatase inhibitors which act to reduce the level of female hormones in the body.
Tamoxifen is typically provided to all oestrogen receptor positive (ER+) patients. However, only around 60% of these patients show a response to tamoxifen, with up to 40% of ER+ tumours failing to respond to or developing resistance to tamoxifen (non-responder subjects).
As tamoxifen is known to increase the risk of endometrial cancer, the provision of tamoxifen to subjects with non-responding tumours (non-responder subjects) needlessly increases the risk of these subjects to the risk of developing endometrial cancer.
Presently, a number of gene array panels are used to try and predict the probability of disease recurrence and determine the most suitable treatment for patients. One such gene panel is known as Oncotype DX. This gene panel cannot be used to select women for tamoxifen therapy. It only predicts recurrence in patients treated with tamoxifen and whether they would be likely to benefit from adjuvant chemotherapy. The assay requires formalin-fixed paraffin embedded (FFPE) tissue. A further panel known as the MammaPrint measures breast cancer recurrence independent of treatment. This panel requires fresh tissue composed of a minimum of 30% malignant cells.
Oncotype DX measures RNA levels of 21 genes (16 cancer genes and 5 reference genes) which demonstrate a consistent statistical link to distant breast cancer recurrence, as well as robust predictive power regarding chemotherapy benefit. MammaPrint measures RNA levels of 70 genes that are considered most informative regarding likelihood of tumour recurrence. Both these assays require expensive, sophisticated equipment.
Accurate prediction of a subject's response to endocrine therapy, would prevent potential non responders being treated with potentially harmful drugs when these may not provide a therapeutic benefit. In addition the determination of those cancer patients which would benefit from endocrine therapy, such as tamoxifen therapy, would allow targeting of such drug regimens and thus may provide for a reduction of healthcare budgets.
Furthermore, the ability to make predictions about cancer progression/disease free survival would enable the design of specific treatment strategies to prevent for example, metastasis following surgery and chemotherapy/endocrine therapy.